Sample analyzing apparatus

ABSTRACT

Provided is a sample analyzing apparatus with which multiple analyses can be performed at the same time in a rapid and accurate manner using a small quantity of a liquid to be measured. This biochemical analyzing apparatus (50) is provided with a chip holder (53) into which an analysis chip (10) can be installed, a chip holder rotation unit (54) for rotating the chip holder (53), a pipetting unit (90) for injecting a candidate liquid into injection ports (22) in the analysis chip (10), and a measurement unit (80) capable of collectively measuring the respective reactions of the candidate liquid and multiple types of antigens (30). The chip holder (53) is rotated by the chip holder rotation unit (54), and injection of the candidate liquid is performed by the pipetting unit (90).

TECHNICAL FIELD

The present invention relates to a sample analysis device used foranalyzing target liquid.

BACKGROUND ART

Some sample analysis devices conventionally known analyze liquid itself.Other sample analysis devices conventionally known analyze target liquidprepared by dispersing or dissolving an analysis target, for example,with at least one or more reactants to react with the target liquidbeing stored in a plurality of storage parts of one reaction container.Patent document 1 discloses a container of this type. The reactioncontainer disclosed in patent document 1 is configured integrally with aplurality of storage parts opened at the upper surface of a substrateand allowing storage of a reagent. Further, at least two of the storageparts are formed independently and configured so as to be capable ofcommunicating with each other.

A sample analysis device requires a constant amount of target liquid foranalysis. Meanwhile, if the target liquid is body fluid or blood, etc.to be taken from a living being including a human body, it is preferablethat the target liquid be as little as possible in consideration of aburden on a biological body. According to an existing method ofconducting analysis using a small amount of target liquid, reactionbetween a reactant and the target liquid is measured using a micro-flowpath into which the target liquid is introduced by means of capillaryaction. Patent documents 2 and 3 disclose a method or a device usingsuch a micro-flow path. Patent document 2 discloses a nozzle cartridgefunctioning as a container storing a reagent or an analyte. This nozzlecartridge includes a storage part for a reagent or an analyte, adischarge nozzle, and a flow path through which the reagent or theanalyte stored in the storage part is supplied to the discharge nozzle.Patent document 3 discloses a micro chemical chip formed of a firstsubstrate having a sample inlet, a second substrate having a sample flowpath, and a third substrate having a sample outlet. The sample inlet isformed as a hole penetrating the first substrate from front to back. Thesample flow path is formed as a slit penetrating the second substratefrom front to back. The sample outlet is formed as a hole penetratingthe third substrate from front to back. The second substrate is arrangedbetween the first and third substrates. The sample inlet and the sampleoutlet communicate with each other through the sample flow path. Thesample flow path is opened on at least one end thereof.

A sample analysis device is required to pipette target liquid into ananalysis chip. Patent documents 4 and 5 disclose mechanisms of pipettingof this type. Patent document 4 discloses a pipetting device thatdischarges liquid into the inside of a well having an opening at one endand allowing storage of liquid therein. The well is formed in amicrochip in which a micro-flow path communicating with an opposite endof the well is formed. The well has a well bottom formed of an annularstepped part projecting inwardly toward the opposite end. This pipettingdevice includes: a pipetting nozzle with a tip opening and a rear end towhich a pipe is connected, the pipetting nozzle sucking and dischargingliquid through the tip opening; movement means that moves pump means andthe pipetting nozzle relative to each other at least in the depthdirection of the well, the pump means being connected to the pipe andsupplying suction pressure and discharge pressure to the pipettingnozzle; and control means that makes the movement means move thepipetting nozzle until the tip opening is located at the well bottom andthen discharges liquid first through the tip opening while making thetip opening contact the bottom surface and/or inner peripheral surfaceof the well bottom. Patent document 5 discloses a method of pipetting aminute amount of liquid into a container through a pipette. According tothis method, a given amount of the liquid is dripped into the containerwhile abutting contact is made between the tip of the pipette and aperipheral wall inside the container.

Patent Document 1: Japanese Unexamined Patent Application, PublicationNo. 2007-189975

Patent Document 2: Japanese Unexamined Patent Application, PublicationNo. 2008-185504

Patent Document 3: PCT International Publication No. WO2012/001972

Patent Document 4: Japanese Unexamined Patent Application, PublicationNo. 2008-76275

Patent Document 5: Japanese Unexamined Patent Application, PublicationNo. S58-137733

DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention

For measuring a plurality of components in target liquid, reactantscorresponding to these components should be stored in a container. Inthis regard, the configurations disclosed in patent documents 2 and 3are expected to achieve the effect of restricting the amount of targetliquid. However, these configurations still find it difficult to analyzeitems such as tens of types of items by one measurement.

It is preferable that, if an analysis chip with a micro-flow path to beused has a configuration where a plurality of micro-flow paths isconnected to an injection port, liquid be introduced uniformly into allof these micro-flow paths. If the aforementioned method of using ananalysis chip with a micro-flow path employs the ELISA (enzyme linkedimmunosorbent assay) process, for example, target liquid should beinjected several times into the micro-flow path during the course ofmeasurement for example of a reaction result. Injecting target liquidseveral times accurately and rapidly leads to reduction in measurementtime. However, further improvement has still been desired for aconventional sample analysis device such as those disclosed in patentdocuments 4 and 5 in terms of introducing liquid uniformly and rapidlyinto micro-flow paths.

The present invention is intended to provide a sample analysis devicecapable of conducting analysis of a plurality of items rapidly andaccurately using a small amount of liquid as a measurement target.

Means for Solving the Problems

The present invention relates to a sample analysis device comprising: achip holder that allows installation of an analysis chip on the chipholder, the analysis chip comprising a substrate, an injection portformed at the substrate and through which target liquid as a measurementtarget is injected, and a flow path connected to the injection port andallowing introduction of the target liquid into the flow path by meansof capillary action, a plurality of reactants capable of selectivelyreacting with a component in the target liquid being fixed to the flowpath; a chip holder rotation mechanism that rotates the chip holder; apipetting mechanism that injects the target liquid into the injectionport of the analysis chip; and a measurement device that allowsmeasurement of reactions between the target liquid and the plurality ofreactants, wherein the pipetting mechanism injects the target liquidwhile the chip holder rotation mechanism rotates the chip holder.

Preferably, the pipetting mechanism has a tip portion of a taperedshape, and the pipetting mechanism injects the target liquid with thetip portion being inserted into the injection port.

Preferably, the injection port of the analysis chip is formed at thecenter of the substrate.

Preferably, the flow path of the analysis chip includes a plurality offlow paths arranged in a radial pattern to extend from the injectionport to an outer edge of the substrate, and the plurality of reactantscapable of selectively reacting with a component in the target liquid isfixed to each of the flow paths.

Preferably, the analysis chip is formed in such a manner that the flowpath surrounds the injection port.

Preferably, the sample analysis device further comprises an airinjection mechanism that injects air into the injection port of theanalysis chip.

Preferably, the air injection mechanism injects air into the analysischip while the chip holder is rotated.

Preferably, the analysis chip further comprises a housing in which thesubstrate is arranged and housed, and the housing includes: an openingpart where an upper surface of the substrate is exposed at leastpartially; liquid trapping space provided inside the housing and on anouter peripheral side of the substrate; and a communication openingformed around the opening part and between the upper surface of thesubstrate and the housing.

Preferably, the communication opening is arranged inwardly in a radialdirection from the outer periphery of the substrate.

Effects of the Invention

Analysis of a plurality of items about liquid as a measurement targetcan be conducted rapidly and accurately by the sample analysis deviceaccording to the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an analysis chip according to anembodiment of the present invention;

FIG. 2 is a perspective view illustrating the configuration of theanalysis chip;

FIG. 3 is a plan view of the analysis chip;

FIG. 4 is a sectional view taken along a line A-A of FIG. 3;

FIG. 5 illustrates a part B of FIG. 1 in an enlarged manner;

FIG. 6 is a plan view of a substrate schematically illustrating anantigen as a reactant fixed to a micro-flow path;

FIG. 7 is an enlarged view schematically illustrating antigens asreactants adjacent to each other in the micro-flow path;

FIG. 8 is a perspective view of a biochemical analysis device accordingto the embodiment of the present invention;

FIG. 9 is a perspective view illustrating the inside of the biochemicalanalysis device in outline;

FIG. 10 is a plan view illustrating the inside of the biochemicalanalysis device in outline;

FIG. 11 is a plan view of a chip holder illustrating a state where apipetting unit is injecting target liquid into the analysis chip;

FIG. 12 is a block diagram schematically illustrating a relationshipbetween a control unit and each structure;

FIG. 13 illustrates an example of analysis image information acquired bya measurement unit;

FIG. 14 is a flowchart of measurement and analysis conducted by thebiochemical analysis device according to the embodiment of the presentinvention;

FIG. 15 is a schematic view illustrating a state in outline where apipetting unit of a biochemical analysis device according to amodification is injecting target liquid into the analysis chip;

FIG. 16 is a plan view illustrating an analysis chip according to amodification; and

FIG. 17 is a side sectional view schematically illustrating theconfiguration of the inside of the analysis chip according to themodification.

PREFERRED MODE FOR CARRYING OUT THE INVENTION

A preferred embodiment of a biochemical analysis device as a sampleanalysis device of the present invention and a preferred embodiment ofan analysis chip of the present invention are described below byreferring to the drawings.

In this embodiment, a biochemical analysis device 50 that determines anallergy of an analyte as target liquid by means of chemiluminescenceresulting from antigen-antibody reaction by employing the ELISA processand an analysis chip 10 used in the biochemical analysis device 50 aredescribed as an example of a sample analysis device and an example of ananalysis chip of the present invention respectively.

The analysis chip 10 of this embodiment is described. FIG. 1 is aperspective view of the analysis chip 10 according to the embodiment ofthe present invention. FIG. 2 is a perspective view illustrating theconfiguration of the analysis chip 10. FIG. 3 is a plan view of theanalysis chip 10. FIG. 4 is a sectional view taken along a line A-A ofFIG. 3. FIG. 5 illustrates a part B (an area surrounded by a dashed lineof FIG. 1) in an enlarged manner. FIG. 6 is a plan view of a substrateschematically illustrating an antigen 30 as a reactant fixed to amicro-flow path 23. FIG. 7 is an enlarged view schematicallyillustrating antigens 30 as reactants adjacent to each other in themicro-flow path 23.

As illustrated in FIG. 1, the analysis chip 10 of this embodiment has anouter shape formed into a substantially disc shape. As illustrated inFIGS. 2 to 4, the analysis chip 10 includes a substrate 20, a film 14, alower housing 12, an upper housing 13, an absorber 15, liquid trappingspace 16, and an air communication opening 17.

The substrate 20 is formed into a substantially disc shape using alight-transmitting material such as cyclic polyolefin. As illustrated inFIG. 6, the antigen 30 to specifically react with a target substancecontained in an analyte (target liquid) as a measurement target is fixedto the substrate 20.

The substrate 20 of this embodiment includes an injection port 22 and amicro-flow path 23. The antigen 30 as a reactant is fixed to thesubstrate 20.

The substrate 20 is formed into a disc shape. The configuration of thesubstrate 20 is described. The substrate 20 has a through hole to becomethe injection port 22. The substrate 20 has a lower surface providedwith a plurality of slits equiangularly spaced in a radial pattern withrespect to the injection port 22. Each of these slits has one endportion connected to the injection port 22 and an opposite end portionconnected to an opening part at an outer edge surface of the substrate20. The antigen 30 is fixed to the bottom surface of each slit. The film14 described later is attached to a surface of the substrate 20 providedwith the slit. In this way, in this embodiment, the slit formed in thesubstrate 20 is closed by the film 14 and the slit in the substrate 20and the film 14 form the micro-flow path 23.

The injection port 22 is used for introducing target liquid such as ananalyte or a reagent solution into the micro-flow path 23. The injectionport 22 is located at a substantially central position of the substrate20 formed into a substantially disc shape. The injection port 22communicates with each of a plurality of micro-flow paths 23 inside thesubstrate 20.

The micro-flow path 23 is a capillary having one end communicating withthe injection port 22 inside the substrate 20 and an opposite endpenetrating the substrate 20 to reach as far as an outer edge of thesubstrate 20 in a radial direction. As illustrated in FIG. 6, themicro-flow path 23 includes a plurality of micro-flow paths 23 extendingfrom the injection port 22 and being equiangularly spaced in a radialpattern. The substrate 20 of this embodiment includes eight micro-flowpaths 23.

The micro-flow path 23 is configured in such a manner that liquid isintroduced into space inside the micro-flow path 23 by means ofcapillary action. For example, in this embodiment, based on theviscosity of a blood analyte as target liquid and a result ofverification, the micro-flow path 23 is set to have a width of 0.1 mm ormore and 3 mm or less and a height of 0.1 mm or more and 0.5 mm or less.

As described above, the antigen 30 is fixed to the inner wall of themicro-flow path 23. The antigen 30 includes a plurality of antigens 30fixed so as to be aligned linearly in a lengthwise direction of eachmicro-flow path 23. As illustrated in FIG. 6, the antigens 30 are eachfixed in the form of a spot having a diameter smaller than a widthbetween wall surfaces of the micro-flow path 23. The antigens 30 fixedto the wall surfaces of the micro-flow path 23 do not extend over thewall surfaces entirely but they exist as spots on the wall surfaces. Bydoing so, an area occupied by the fixed antigens 30 can be controlled ata minimum required area. This reduces the probability of contaminationor reaction nonuniformity to occur if a large area is occupied by thefixed antigens 30. During measurement of light-emitting reactiondescribed later, fixing the antigens 30 in the form of small-diameterspots as in this embodiment also effectively reduces the probability ofinterference between light beams resulting from light-emitting reactionsgenerated in adjacent micro-flow paths 23, compared to fixing antigensto the entire region of the micro-flow path 23. In this embodiment, aswill also be described later, a camera unit 83 captures an image of anantigen 30 from above where light-emitting reaction is generated,thereby acquiring image information. Thus, light-emitting reaction atone antigen 30 in the form of a small-diameter spot 30 should be assuredin a sufficient condition with in-plane uniformity for distinguishingthis antigen 30 from a different light-emitting antigen 30 andpreventing interference between light beams from these antigens 30. Forthis purpose, to direct light resulting from light-emitting reaction andto travel toward an image-capturing element mainly in a directionsubstantially perpendicular to the micro-flow path 23, the upper surfaceof the antigen 30 in the form of a spot is formed as a substantiallysmooth surface. This is achieved by controlling the antigen 30 in termsof its viscosity, etc. or forming the antigen 30 by pressing into asmooth shape with a tool such as a stamp, for example.

The antigens 30 are arranged at given intervals. As illustrated in FIG.7, a distance d between adjacent antigens 30 is set in such a mannerthat light beams emitted from antigens 30 in adjacent positions do notinterfere with each other during measurement of light-emitting reaction.In this embodiment, the adjacent antigens 30 should be formed atpositions separated from each other by the distance d that is 60% ormore of the diameter of an antigen 30 having a smallest diameter ofthose of the antigens 30 fixed to the micro-flow path 23.

The antigens 30 are various types of allergens to specifically reactwith a selected component (target substance) in an analyte. In thisembodiment, eight micro-flow paths 23 are formed in the substrate 20.Five antigens 30 are aligned substantially linearly while beingseparated by the aforementioned given distance d in each of themicro-flow paths 23. To reliably measure reactions of a plurality ofantigens 30 fixed to the substrate 20, antigens of the same type may bearranged at a plurality of micro-flow paths or at different positions.Alternatively, antigens of types different from each other may be used.In this case, many pieces of analysis information can be acquiredcollectively.

The substrate 20 of this embodiment has the aforementionedconfiguration. The configuration of the substrate 20 is not limited tothe aforementioned configuration but can be changed, if appropriate, ina manner that depends on the purpose of the substrate 20. For example,the number of the micro-flow paths 23 may be changed or the micro-flowpaths 23 may be arranged at unequal angles. Further, the antigen 30 isdescribed as an example of a reactant fixed to the substrate 20.Alternatively, an antibody may be fixed.

The film 14 is formed into a substantially circular thin-film shape andattached to the lower surface of the substrate 20 as described above.The substrate 20 is arranged over the upper surface of the lower housing12 through the film 14.

The lower housing 12 is arranged on a lower surface (one surface) sideof the substrate 20 and formed into a substantially circular shapehaving an outer periphery of a larger diameter than the substrate 20.The lower housing 12 is provided with a wall part extending along theouter periphery of the lower housing 12 to form a lower part of theperipheral surface of the analysis chip 10.

The upper housing 13 is arranged on an upper surface (opposite surface)side of the substrate 20. The upper housing 13 is formed into asubstantially ring-like shape having an outer periphery of a largerdiameter than the substrate 20. The upper housing 13 has an opening part18 formed at the center of the upper housing 13 and having a circularshape of a smaller diameter than the substrate 20. The upper housing 13is provided with a wall part extending along the outer periphery of theupper housing 13 to form an upper part of the peripheral surface of theanalysis chip 10. A housing of the analysis chip 10 of this embodimentis formed of the lower housing 12 and the upper housing 13.

The absorber 15 is formed of a member having moisture-retainingproperties. The absorber 15 is formed into a ring-like shape of asmaller diameter than the lower housing 12 and the upper housing 13 andarranged in the liquid trapping space 16. Liquid having been dischargedfrom the micro-flow path 23 is absorbed by the absorber 15. In the caseof biochemical analysis, for example, discharge of liquid targeted foranalysis from an analysis device to the outside of a system shouldstrictly be avoided. For this reason, the absorber 15 is provided alongthe outer periphery of the substrate 20.

As illustrated in FIG. 4, the liquid trapping space 16 is defined by thelower housing 12 and the upper housing 13 into ring-like spacesurrounding the outer periphery of the substrate 20. An opening part ofthe micro-flow path 23 on an outer edge side formed in the peripheralsurface of the substrate 20 is opened to the liquid trapping space 16.Thus, as will be described later, target liquid discharged from theopening part of the micro-flow path 23 is discharged to the liquidtrapping space 16. The target liquid having been discharged to theliquid trapping space 16 is absorbed by the absorber 15 arranged in theliquid trapping space 16. Further, the discharged target liquid achievesthe action of moisturizing the liquid trapping space 16 and themicro-flow path 23 in the substrate 20.

As illustrated in FIG. 5, the air communication opening 17 is defined atan inner opening wall of the upper housing 13 by the upper surface ofthe substrate 20 and the upper housing 13. The air communication opening17 includes a plurality of air communication openings 17 arranged atsubstantially regular intervals. As illustrated in FIG. 3, in the radialdirection of the substrate 20, the air communication opening 17 isformed slightly inwardly from an opening of the micro-flow path 23provided at the outer edge of the substrate 20 and close to the liquidtrapping space 16. By the presence of the air communication opening 17,the injection port 22 of the substrate 20 and external space communicatewith each other through the micro-flow path 23. Thus, air having beeninjected through the injection port 22 by an air nozzle unit 100 in anair injecting process described later is discharged from the aircommunication opening 17 to external space through the micro-flow path23. In the radial direction of the substrate 20, the air communicationopening 17 is arranged inwardly from the opening as a liquid dischargeopening of the micro-flow path 23 close to the liquid trapping space 16.This prevents liquid discharged from the micro-flow path 23 from beingdischarged to the outside of the system of the analysis chip 10 throughthe air communication opening 17.

The analysis chip 10 of this embodiment has the aforementionedconfiguration. The following description is about the biochemicalanalysis device 50 that analyzes target liquid using the analysis chip10 of this embodiment. FIG. 8 is a perspective view of the biochemicalanalysis device 50 according to the embodiment of the present invention.FIG. 9 is a perspective view illustrating the inside of the biochemicalanalysis device 50 in outline. FIG. 10 is a plan view illustrating theinside of the biochemical analysis device 50 in outline. FIG. 11 is aplan view of a chip holder 53 illustrating a state where a pipettingunit 90 is injecting target liquid into the analysis chip 10. FIG. 12 isa block diagram schematically illustrating a relationship between acontrol unit 110 and each structure. FIG. 13 illustrates an example ofanalysis image information acquired by a measurement unit 80.

As illustrated from FIGS. 8 to 12, the biochemical analysis device 50includes a housing 51, a touch panel 52, a chip holder rotation unit 54,the measurement unit 80, the pipetting unit 90, the air nozzle unit 100,a reagent holder unit 58, and the control unit 110.

The housing 51 houses each structure of the biochemical analysis device50 and separates internal mechanisms for analysis and external space.The housing 51 is provided with a door 55.

The touch panel 52 functions both as operation means and display meansof the biochemical analysis device 50. The touch panel 52 is used formaking various settings and performing various operations, and fordisplaying a measurement result and an analysis result, for example.

The chip holder rotation unit 54 rotates the analysis chip 10. In thisembodiment, an injecting process of injecting target liquid into theanalysis chip 10 and a discharging process for liquid having beenintroduced into the micro-flow path 23 are performed by making the chipholder rotation unit 54 rotate the analysis chip 10. The configurationof the chip holder rotation unit 54 is described below.

The chip holder rotation unit 54 of this embodiment includes the chipholder 53, a chip holder drive motor, a temperature adjustment unit, anda temperature sensor.

The chip holder 53 is installed at an upper part of the chip holderrotation unit 54. The chip holder 53 includes a fitting part 531 to makea fit with the analysis chip 10. The fitting part 531 is formed at theupper surface of the chip holder 53 and functions as a frame part tocontact a portion of the peripheral surface of the analysis chip 10. Asillustrated in FIG. 11, with the analysis chip 10 placed at the chipholder 53, the fitting part 531 holds a portion of the outer peripheryof the analysis chip 10 to prevent falling off of the analysis chip 10from the chip holder 53 to be caused by centrifugal force.

The fitting part 531 is configured to make a fit with the analysis chip10 in such a manner that the center of the injection port 22 of theanalysis chip 10 and the center of rotation of the chip holder 53substantially agree with each other. The analysis chip 10 is configuredto be placed in a substantially horizontal posture while being installedat the chip holder 53.

The analysis chip 10 and the fitting part 531 can also be configured asfollows. An analysis chip fitting part with a protrusion, a recess, or aprotrusion and a recess is formed at the lower surface of the analysischip 10 (lower surface of the lower housing 12). Then, a shapeconforming to the shape of the analysis chip fitting part is formed at asurface of the fitting part 531 to contact the lower surface of theanalysis chip 10. This can make a fit between the analysis chip 10 andthe fitting part 531 more reliably, while making it possible to adjustthe rotation speed of the analysis chip 10 more properly. Additionally,as a result of increase in the area of contact between the analysis chip10 and the fitting part 531, heat of the analysis chip 10 can beadjusted more easily by the temperature adjustment unit through the chipholder 53 in an incubation process described later, thereby achievingefficient temperature adjustment. In consideration of expansion orcompression of the chip holder 53 by heat during incubation, the shapesformed at the analysis chip fitting part and the fitting part 531 may beshapes that can be detached from each other easily such as a mountainshape and a valley shape, teeth-like shapes, conical shapes, orcorrugated shapes, for example.

The chip holder drive motor is arranged inside the chip holder rotationunit 54 and has a drive shaft coupled to the rotary shaft of the chipholder 53 (not illustrated in the drawings). The chip holder drive motoris configured to rotate at a frequency that can be adjusted at anyvalue. The chip holder rotation unit 54 is electrically connected to thecontrol unit 110. Based on a signal from the control unit 110, the chipholder rotation unit 54 adjusts the rotation frequency of the chipholder drive motor to rotate the chip holder 53 at a given speed. Inthis embodiment, the chip holder 53 is configured to rotate at a speedthat can be switched between an injection rotation speed described laterand a liquid discharge speed described later.

The injection rotation speed is a rotation speed of the chip holder 53employed when the pipetting unit 90 injects liquid into the injectionport 22 of the analysis chip 10.

The liquid discharge speed is a rotation speed employed when liquidhaving been introduced into the micro-flow path 23 of the analysis chip10 is discharged from the micro-flow path 23 to the liquid trappingspace 16. To discharge liquid from the micro-flow path 23 by means ofcentrifugal force, the liquid discharge speed of this embodiment is setso as to rotate the chip holder 53 at a speed higher than the injectionrotation speed that does not cause discharge of liquid having beenintroduced into the micro-flow path 23.

The temperature adjustment unit is arranged inside the chip holderrotation unit 54 and configured to achieve temperature adjustment of theanalysis chip 10 installed at the chip holder 53 (not illustrated in thedrawings). By the presence of the temperature adjustment unit,pre-incubation and incubation for generating reaction between theantigen 30 and target liquid proceed properly.

The temperature sensor is arranged inside the chip holder rotation unit54 (not illustrated in the drawings). Temperature information acquiredby the temperature sensor is transmitted to the control unit 110. Thecontrol unit 110 is configured in such a manner that the control unit110 can adjust warming by the temperature adjustment unit based on theacquired temperature information.

The measurement unit 80 is described next. The measurement unit 80measures light-emitting reaction. The measurement unit 80 includes adark box 81, a chip holder movement mechanism 82, the camera unit 83,and an LED unit.

The dark box 81 is configured as a hermetically-sealed rectangularparallelepiped. The dark box 81 functions as a dark box for shieldinglight from the outside of the system during measurement and as atemperature adjusting chamber for heat retention during pre-incubationand incubation. The dark box 81 has an opening part at one side surface.

The chip holder movement mechanism 82 includes drive means (notillustrated in the drawings) arranged at the opening part of the darkbox 81 and used for moving the chip holder rotation unit 54. The chipholder movement mechanism 82 allows the chip holder rotation unit 54 tomove between a liquid injection position, an air injection position, anda measurement position.

The liquid injection position of the chip holder rotation unit 54 is aposition employed when the pipetting unit 90 injects liquid into theanalysis chip 10. The chip holder rotation unit 54 at the liquidinjection position is arranged outside the dark box 81 (in the state ofFIGS. 9 and 10). The air injection position of the chip holder rotationunit 54 is a position employed when the air nozzle unit 100 injects airinto the analysis chip 10.

The measurement position of the chip holder rotation unit 54 is aposition employed when the measurement unit 80 measures the analysischip 10 inside the dark box 81. The measurement position is such thatthe opening part of the dark box 81 is closed in response to movement ofthe chip holder rotation unit 54 to hermetically seal the dark box 81.

The camera unit 83 is arranged above the dark box 81. The camera unit 83is a measurement unit (image capturing unit) to capture an image of theanalysis chip 10 from above at the measurement position. Variousdeterminations are made based on image information resulting from imagecapturing by the camera unit 83. The exposure time of the camera unit 83of this embodiment is adjusted based on an experimental result, etc., soas to allow detection of emission of very weak light. A member forreducing influence of reflected light such as a polarizing plate may bearranged inside the dark box 81.

The measurement unit 80 makes the camera unit 83 capture an image of theanalysis chip 10 at the measurement position where light-emittingreaction is generated, thereby acquiring image information asmeasurement information. As illustrated in FIG. 13, the camera unit 83acquires information about an image with a resolution by which theposition of light-emitting reaction can be identified clearly. Thecamera unit 83 includes the LED unit.

The LED unit is an illumination device for illuminating the inside ofthe dark box 81 during image capturing by the camera unit 83.

The measurement unit 80 is electrically connected to the control unit110. The chip holder movement mechanism 82, the camera unit 83, the LEDunit, and the temperature sensor of the measurement unit 80 areconfigured in such a manner as to allow transmission and receipt ofvarious signals to and from the control unit 110. Based on a signal fromthe control unit 110, the measurement unit 80 drives the drive means ofthe chip holder movement mechanism 82 so as to move the chip holderrotation unit 54 to the liquid injection position, the air injectionposition, or the measurement position. A signal from the control unit110 is also used for making the camera unit 83 capture an image or forcontrol over luminosity adjustment by the LED unit, etc.

The pipetting unit 90 is described next. The pipetting unit 90 pipettesliquid (target liquid) into the injection port 22 of the analysis chip10 placed at the chip holder 53. Liquid to be injected into the analysischip 10 by the pipetting unit 90 includes a blocking solution, ananalyte, a cleaning liquid, and a luminescent substrate, for example.

The pipetting unit 90 includes a pipetting casing 91, a pipetting nozzle92, a pipetting nozzle movement mechanism 93, and a pipetting unitmovement mechanism 94.

A detachable pipette chip 95 is attached to the pipetting nozzle 92.Liquid is pipetted into the analysis chip 10 using the pipette chip 95as a tip portion of the pipetting nozzle 92. The pipetting nozzlemovement mechanism 93 moves the pipetting nozzle 92 in a verticaldirection. The pipetting unit movement mechanism 94 moves the pipettingunit 90. The pipetting unit 90 can be moved in a horizontal direction bythe pipetting unit movement mechanism 94. The pipetting unit 90 can movebetween a liquid injection position illustrated in FIG. 11 where thepipetting unit 90 is close to the chip holder 53, and a standby positionillustrated in FIG. 10 where the pipetting unit 90 is separated from thechip holder 53.

The pipetting unit 90 moves the pipetting nozzle 92 between a pipettechip attachment position, a pipette chip detachment position, thestandby position, and the liquid injection position by using thepipetting nozzle movement mechanism 93 and the pipetting unit movementmechanism 94. In the pipetting unit 90, based on a signal from thecontrol unit 110, drive means of each of the pipetting nozzle movementmechanism 93 and the pipetting unit movement mechanism 94 is driven soas to move the pipetting nozzle 92 to the liquid injection position, thepipette chip attachment position, the pipette chip detachment position,or the standby position.

The pipette chip attachment position of the pipetting unit 90 is aposition employed for attaching an unused pipette chip 95 to be placedin the reagent holder unit 58 described later. The pipette chipdetachment position of the pipetting unit 90 is a position employed whena used pipette chip 95 is detached from the pipetting nozzle 92 by apipette chip detachment mechanism (not illustrated in the drawings) ofthe reagent holder unit 58. The standby position is the position of thepipetting nozzle 92 employed while the pipetting unit 90 is moving. Thestandby position is higher than any of the liquid injection position,the pipette chip attachment position, and the pipette chip detachmentposition. The pipetting nozzle 92 is at the standby position while thepipetting unit 90 is moving to cause no interference with movement ofthe pipetting nozzle 92.

The liquid injection position of the pipetting unit 90 is a positionemployed for injection of liquid into the analysis chip 10. The liquidinjection position of this embodiment is set in such a manner that thetip of the pipette chip 95 installed at the tip of the pipetting nozzle92 substantially agrees with the center of rotation of the chip holder53 in a plan view.

The liquid injection position of this embodiment is set in such a mannerthat the tip of the pipette chip 95 is placed at a position below theupper surface of the substrate 20 and not contacting the bottom surfaceof the injection port 22.

An injecting process at the liquid injection position is performed whilethe chip holder 53 rotates at the injection rotation speed. Thepipetting unit 90 injects liquid into the analysis chip 10 continuouslyat a constant speed or in stages. The tip of the pipette chip 95 isplaced below the upper surface of the substrate 20. This preventsflying-off of liquid over the upper surface of the substrate 20 orblockage of the injection port 22 with droplets of target liquid. As aresult, the target liquid of a minute amount can be introduced rapidlyand properly into the micro-flow path 23 through the injection port 22.

As a result of pipetting while rotating the chip holder 53, even if atip portion of the pipette chip 95 deviates from the center of rotation,distances from the tip portion of the pipette chip 95 to a plurality ofthe micro-flow paths 23 can be substantially equal. Thus, liquid isintroduced into these micro-flow paths 23 with substantially equalprobability. This prevents the occurrence of a problem such as failingto introduce liquid properly into some of these micro-flow paths 23.This can effectively reduce influence on the injecting process to beexerted by the accuracy of the shape or attachment condition of the tipportion of the pipetting nozzle 92, particularly in the case where thetip portion of the pipetting nozzle 92 is formed of a disposable pipettechip 95, for example.

A method of injecting liquid into the analysis chip 10 using thepipetting unit 90 can be determined properly in a manner that depends onthe amount of the liquid to be injected. For example, to reduce time ofthe injection, without injecting the liquid in stages, a given amount ofthe liquid may be injected at a time. Alternatively, a speed of theinjection may be changed.

The air nozzle unit 100 is described next. The air nozzle unit 100 isfor auxiliary discharge of liquid with air to the liquid trapping space16 remaining in the micro-flow path 23 of the analysis chip 10 withouthaving been discharged only by centrifugal force resulting fromrotation. The air nozzle unit 100 is arranged above the chip holderrotation unit 54.

The air nozzle unit 100 includes an air nozzle 101 and an air nozzlemovement mechanism 102. In this embodiment, the air nozzle unit 100injects air while the chip holder 53 is rotated at the liquid dischargespeed.

The air nozzle movement mechanism 102 moves the air nozzle 101 betweenan air injection position and a standby position. The air nozzle 101 ismoved between the air injection position and the standby position by theair nozzle movement mechanism 102.

The air injection position is a position employed for injection of airinto the injection port 22 of the analysis chip 10. A tip portion of theair nozzle 101 at the air injection position faces the injection port 22of the analysis chip 10. In this embodiment, the standby position is aposition employed when the air nozzle unit 100 does not inject air. Whenthe air nozzle 101 is at the standby position, the tip portion of theair nozzle 101 is placed above the air injection position and does notface the injection port 22.

At the air injection position, air is injected while the chip holder 53rotates at the liquid discharge speed. Inside the analysis chip 10,liquid remaining in the micro-flow path 23 is discharged to the liquidtrapping space 16 with air injected through the injection port 22. Evenif liquid remains in the micro-flow path 23 by means of capillaryaction, such remaining liquid can reliably be removed from themicro-flow path 23 with the air injected from the air nozzle unit 100.The liquid having been discharged to the liquid trapping space 16 isabsorbed by the absorber 15. The air having exited the micro-flow path23 passes through the air communication opening 17 to be discharged tothe outside the system of the analysis chip 10. As described above, inthe analysis chip 10, the air communication opening 17 is arrangedinwardly in the radial direction from the exit of the micro-flow path23, as illustrated in FIG. 3. This prevents the liquid discharged fromthe micro-flow path 23 from being discharged to the outside of thesystem of the analysis chip 10 through the air communication opening 17,while allowing discharge of the air to the outside of the system of theanalysis chip 10.

In this embodiment, air is injected after rotation of the chip holder 53is started. By doing so, most of liquid is discharged in advance bycentrifugal force from the micro-flow path 23 and thereafter, air isinjected. If liquid is discharged only by means of air injection,discharge of the liquid from a particular micro-flow path 23 may befinished first. In this case, air may exist intensively only in adischarge channel in this micro-flow path 23, thus possibly failing todischarge the liquid from remaining micro-flow paths. Such a problem canbe avoided by discharging most of the liquid in advance by means ofcentrifugal force resulting from rotation of the chip holder 53. In thisway, according to the configuration of this embodiment, every liquid inthe plurality of micro-flow paths 23 can efficiently be discharged.

The reagent holder unit 58 is described next. The reagent holder unit 58is for installation of a reagent cartridge 96 and the pipette chip 95 onthe reagent holder unit 58.

The reagent cartridge 96 stores multiple types of target liquid to beinjected into the analysis chip 10 including a blocking solution, ananalyte, a luminescent substrate, a cleaning liquid, etc. A plurality ofunused pipette chips 95 is placed in the reagent cartridge 96. Thereagent holder unit 58 of this embodiment includes an installation part(not illustrated in the drawings) with which the reagent cartridge 96can be attached and detached. The reagent cartridge 96 is fixed to theinstallation part.

The pipette chip 95 is attached to the pipetting nozzle 92 of thepipetting unit 90. The pipette chip 95 is a disposable chip to bechanged for each liquid to be injected. The reagent holder unit 58 ofthis embodiment includes a disposal housing part 97 for housing a usedpipette chip 95 and the pipette chip detachment mechanism (notillustrated in the drawings). The pipette chip detachment mechanismdetaches a used pipette chip 95 from the pipetting nozzle 92.

The control unit 110 is described next. The control unit 110 is acomputer formed of a CPU, a memory as a storage, etc. As illustrated inFIG. 12, the control unit 110 is electrically connected to the touchpanel 52, the chip holder rotation unit 54, the measurement unit 80, thepipetting unit 90, the air nozzle unit 100, etc. As described above,each unit performs all of or some of its operations in response to asignal from the control unit 110. Specifically, a signal from thecontrol unit 110 is used for controlling a sequence of the biochemicalanalysis device 50, etc. that includes control over rotation speed ofthe chip holder 53, movement of the chip holder rotation unit 54,movement of the pipetting unit 90 and a pipetting process by thepipetting unit 90, air injection by the air nozzle unit 100, imagecapturing by the measurement unit 80, and warming by the temperatureadjustment unit, for example. The control unit 110 is furtherresponsible for image processing, setting and storage of a testcondition, output of analysis data, etc. Exerting control over themeasurement unit 80 by the control unit 110 includes exerting controlover all the structures of the measurement unit 80 including the cameraunit 83, the chip holder movement mechanism 82, and the LED unit.Additionally, exerting control over the chip holder rotation unit 54,the pipetting unit 90, the air nozzle unit 100, and the reagent holderunit 58 includes exerting control over the movement mechanism of each ofthese structures.

In this embodiment, as described above, antigen-antibody reaction ismeasured based on image information acquired as a result of capturing ofan image by the camera unit 83 about light-emitting reaction generatedat the measurement position.

Specificity of reaction with a selected substance is acquired from anantigen 30 exhibiting this light-emitting reaction in the acquired imageinformation. Information for example about the intensity of the reactionspecificity is acquired based on the intensity of the emitted light.

The biochemical analysis device 50 of this embodiment has theaforementioned configuration. A flow of measurement by the biochemicalanalysis device 50 of this embodiment is described next. FIG. 14 is aflowchart of measurement and analysis conducted by the biochemicalanalysis device 50 according to the embodiment of the present invention.

A user of the biochemical analysis device 50 is placed the analysis chip10 at the chip holder 53. Further, the user places the reagent cartridge94 storing an analyte, a reagent solution, a cleaning liquid, thepipette chip 95, etc. at the reagent holder unit 58. Next, the useroperates the touch panel 52 to start measurement at the biochemicalanalysis device 50. In response to receipt of a signal indicating startof the measurement from the touch panel 52, the control unit 110 startscontrol over sequential steps from blocking solution injection in stepS101.

First, the blocking solution injection (S101) is performed to preventnon-specific adsorption of an antibody, etc. to a part in the micro-flowpath 23 other than the antigen 30. The blocking solution injection(S101) is performed by making the pipetting unit 90 inject a blockingsolution through the injection port 22 of the analysis chip 10 while thechip holder 53 is rotated at the injection rotation speed. The blockingsolution having been injected through the injection port 22 isintroduced into the plurality of micro-flow paths 23 formed in a radialpattern with respect to the injection port 22 to extend over themicro-flow paths 23 entirely by means of the aforementioned capillaryaction. After the pipette chip 95 is detached, a pre-incubation process(S102) is performed to fix the injected blocking solution sufficientlyto a part in the micro-flow path 23 other than the antigen 30.

The pre-incubation process (S102) is performed with the chip holder 53having been moved to the inside of the dark box 81 functioning as atemperature adjusting chamber. After the pre-incubation process (S102)is performed for a given period of time, the chip holder 53 is returnedto a position outside the dark box 81. Then, for analyte injection(S104), a liquid discharging process (S103) is performed to dischargethe blocking solution to the outside of the micro-flow path 23 torelease the inside of the micro-flow path 23.

The liquid discharging process (S103) is performed by making the chipholder rotation unit 54 rotate the chip holder 53 at the liquiddischarge speed and making the air nozzle unit 100 inject air throughthe injection port 22 of the analysis chip 10.

The micro-flow path 23 is formed to extend in a direction toward itsouter edge from the center of rotation. The remaining blocking solutionis moved and discharged to the liquid trapping space 16 outside theouter edge of the micro-flow path 23 by centrifugal force, while beingdischarged further with air substantially reliably to the liquidtrapping space 16. As described above, even in the micro-flow path 23where strong surface tension is generated by capillary action, theliquid discharging process can still be performed rapidly andeffectively.

The blocking solution having been discharged from the micro-flow path 23is absorbed by the absorber 15 in the liquid trapping space 16.According to the analysis chip 10 of this embodiment, liquid having beendischarged from the micro-flow path 23 is absorbed by the absorber 15provided in the liquid trapping space 16. This can reliably preventdischarge of target liquid to the outside of the system of the analysischip 10. The target liquid having been discharged to the liquid trappingspace 16 is absorbed by the absorber 15. This prevents the target liquidhaving been discharged from the micro-flow path 23 from flowing backinto the micro-flow path 23, so that subsequent processes are performedproperly.

The analyte injection (S104) is performed by injecting an analyte intothe analysis chip 10 while the chip holder 53 is rotated at theinjection rotation speed. Like in the blocking solution injection(S101), the analyte having been injected through the injection port 22is introduced uniformly into the plurality of micro-flow paths 23 bymeans of capillary action. After the analyte injection (S104), anincubation process (S105) is performed to prompt antigen-antibodyreaction between the antigen 30 and the analyte.

Like the pre-incubation process (S102), the incubation process (S105) isperformed with the chip holder 53 having been moved to the inside of thedark box 81 functioning as a temperature adjusting chamber. Theincubation is performed by making temperature adjustment for a givenperiod of time using the temperature adjustment unit.

The absorber 15 of the analysis chip 10 contains the blocking solutionalready absorbed as a result of the liquid discharging process for theblocking solution (S103), so that the inside of the analysis chip 10 hasalready been humidified. This prevents drying of the inside of themicro-flow path 23 during the incubation (S105). Then, the chip holder53 is taken out of the dark box 81 to proceed to a liquid dischargingprocess for the analyte (S106).

Like the liquid discharging process for the blocking solution (S103),the liquid discharging process for the analyte (S106) is performed byrotating the chip holder 53 at the liquid discharge speed and making theair nozzle unit 100 inject air. As a result of this liquid dischargingprocess (S106), the analyte in the micro-flow path 23 is discharged tothe liquid trapping space 16 and absorbed by the absorber 15. After theinside of the micro-flow path 23 is released by this liquid dischargingprocess for the analyte, a cleaning process (S107) is performed.

Like the blocking solution injection (S101), the cleaning process (S107)is performed by rotating the chip holder 53 at the injection rotationspeed and injecting a cleaning liquid through the injection port 22 ofthe analysis chip 10 and introducing the cleaning liquid into theplurality of micro-flow paths 23 formed in a radial pattern with respectto the injection port 22. Next, like the liquid discharging process forthe blocking solution (S103), a liquid discharging process for thecleaning liquid is performed by making the chip holder rotation unit 54rotate the chip holder 53 at the liquid discharge speed and making theair nozzle unit 100 inject air. By performing the aforementionedcleaning process of injecting and discharging the cleaning liquid, theliquid remaining in the plurality of micro-flow paths 23 of thesubstrate 20 is discharged together with the cleaning liquid. Thecleaning liquid is also absorbed by the absorber 15 provided in theliquid trapping space 16. After the cleaning process (S107), labeledantibody injection (S108) of deriving a luminescent substrate by meansof enzyme reaction is performed. The luminescent substrate is used for afinal process of measuring light emission and to be added to the antigen30 where the antigen-antibody reaction is generated by the incubation(S105).

Like the blocking solution injection (S101), the analyte injection(S104), or the cleaning liquid injection (S107), the labeled antibodyinjection (S108) is performed by injecting a labeled antibody androtating the chip holder 53 at the injection rotation speed. Like theincubation (S105) performed to prompt antigen-antibody reaction,incubation (S109) is performed after the injection of the labeledantibody to add the labeled antibody reliably to the antigen 30 wherethe antigen-antibody reaction is generated. Next, a liquid dischargingprocess for the labeled antibody (S110) is performed.

A cleaning process for the labeled antibody (S111) is similar to thecleaning process in step S107 and is performed by injecting anddischarging a cleaning liquid. The cleaning process (S111) includinginjection and discharge of the cleaning liquid is repeated severaltimes, where necessary, thereby obtaining reliable cleaning effect.After the cleaning process (S111), a process of luminescent substrateinjection (S112) is performed.

Like the blocking solution injection (S101), the analyte injection(S104), or the cleaning liquid injection (S107), the luminescentsubstrate injection (S112) is performed by injecting the luminescentsubstrate into the chip holder 53 rotated at the injection rotationspeed. After the luminescent substrate injection (S112), a measuringprocess (S113) is performed.

The measuring process (S113) is performed by making the camera unit 83of the measurement unit 80 capture an image of the analysis chip 10. Thepresence or absence of light emission and the intensity of the emittedlight at each antigen 30 indicating a result of the measurement can bedisplayed for example on the touch panel 52, stored in the storage ofthe control unit 110, transmitted to an external computer connectedthrough wired or wireless communication, or output from an output devicesuch as a printer.

A determining process (S114) is performed on all types of antigens 30(in this embodiment, 40 types). In the determining process (S114), basedon the type of the antigen 30 generating light-emitting reactionunderstood from a result of the measurement obtained in the measuringprocess (S113), specificity of reaction of the analyte with each antigen30 is determined and the intensity of the reaction specificity isdetermined based on the intensity of the emitted light. As describedabove, the analysis chip 10 and the biochemical analysis device 50according to this embodiment achieve measurement of a large number ofitems of as many as 40 types collectively and simultaneously within ashort length of time.

The analysis chip 10 of this embodiment described above achieves thefollowing effects.

The analysis chip 10 of this embodiment includes: the substrate 20formed into a substantially disc shape; the injection port 22 formed atthe center of the substrate 20 and through which target liquid as ameasurement target is injected; and the plurality of micro-flow paths 23formed in a radial pattern to extend from the injection port 22 to theouter edge of the substrate 20 and allowing introduction of the targetliquid into the micro-flow paths 23 by means of capillary action.Multiple types of antigens 30 to selectively react with a component inthe target liquid are fixed to each of the micro-flow paths 23 to bespaced from each other. In this way, multiple types of antigens 30 arefixed to one micro-flow path 23. This makes it possible to makemeasurement of a plurality of items at a time, while restricting arequired amount of the target liquid. Additionally, by forming themicro-flow paths 23 in a radial pattern, the target liquid remaining inthe micro-flow paths 23 can be discharged from the micro-flow paths 23by means of centrifugal force. This works effectively, particularly insample analysis of repeating processes of injecting and dischargingmultiple types of liquid several times during the course of measurement,like in this embodiment.

In the analysis chip 10, the antigen 30 is fixed in the form of a spotto the micro-flow path 23. This makes it possible to arrange a largenumber of antigens 30 in a limited area.

In the analysis chip 10, the antigen 30 fixed to the micro-flow path 23has a shape like a thin film having a flat upper surface. By doing so,for acquiring image information by making the camera unit 83 capture animage of the analysis chip 10 from above, the upper surface of theantigen 30 is formed so as to direct light (optical axis) resulting fromlight-emitting reaction mainly in a direction substantiallyperpendicular to the micro-flow path 23. This prevents interference witha different light-emitting antigen 30, so that an image oflight-emitting reaction can favorably be captured.

The analysis chip 10 further includes a housing in which the substrate20 is arranged and housed and formed of the lower housing 12 and theupper housing 13. The housing includes the opening part 18 where theupper surface of the substrate 20 is exposed at least partially, and theliquid trapping space 16 provided inside the housing and on an outerperipheral side of the substrate 20. This prevents target liquid havingbeen discharged from the micro-flow path 23 from being discharged to theoutside of the system of the analysis chip 10 at the liquid trappingspace 16 inside the housing, while allowing injection of liquid throughthe opening part 18 from above the substrate 20 and allowing imagecapturing by the camera unit 83. The forgoing can be rephrased asfollows. The analysis chip 10 of this embodiment further includes: thelower housing 12 formed into a larger diameter than the substrate 20;the upper housing 13 having the opening part 18 and being formed into alarger diameter than the substrate 20; and the liquid trapping space 16formed on the outer peripheral side of the substrate 20 using the lowerhousing 12 and the upper housing 13. Thus, target liquid having beendischarged from the micro-flow path 23 is trapped in the liquid trappingspace 16, so that the target liquid can be prevented from flowing out ofthe analysis chip 10. This works effectively, particularly in thebiochemical analysis device 50 required to avoid diffusion or leakage ofan analyte taken from a biological body into and out of the biochemicalanalysis device 50.

The analysis chip 10 further includes the absorber 15 arranged in theliquid trapping space 16 and formed of a member havingmoisture-retaining properties. Thus, target liquid having beendischarged to the liquid trapping space 16 is absorbed by the absorber15. This achieves the action of moisturizing the liquid trapping space16 and the micro-flow path 23 in the substrate 20, while preventing thetarget liquid having been discharged from the micro-flow path 23 fromflowing back into the micro-flow path 23.

The analysis chip 10 includes the air communication opening 17 formedaround the opening part 18 and between the upper surface (surface closeto the opening part 18) of the substrate 20 and the upper housing 13.This establishes a passage extending from the injection port 22 to theair communication opening 17 through the micro-flow path 23 for air fromthe air nozzle unit 100, so that liquid in the micro-flow path 23 caneffectively be discharged to the outside of the micro-flow path 23 byinjection of air into the injection port 22.

The injection port 22 of the analysis chip 10 is formed at asubstantially central position of the substrate 20. This makes itpossible to introduce liquid substantially uniformly into the pluralityof micro-flow paths 23 connected to the injection port 22.

The micro-flow paths 23 of the analysis chip 10 are formed in a radialpattern to extend from the injection port 22 to the outer edge of thesubstrate 20. This makes it possible to effectively discharge liquid inthe micro-flow paths 23 by means of centrifugal force resulting fromrotation of the chip holder 53.

The air communication opening 17 of the analysis chip 10 is arrangedinwardly in the radial direction from the opening of the micro-flow path23 formed at the outer edge of the substrate 20 and where liquid isdischarged to the liquid trapping space 16. Specifically, the aircommunication opening 17 is located inwardly in the radial directionfrom the exit of the micro-flow path 23 (outer opening part in theradial direction). As a result, liquid having been discharged to theoutside of the radial direction from the micro-flow path 23 is preventedfrom leaking to the outside of the analysis chip 10 through the aircommunication opening 17.

The biochemical analysis device 50 of this embodiment described aboveachieves the following effects.

The biochemical analysis device 50 includes: the chip holder 53 thatallows installation of the analysis chip 10 on the chip holder 53; thechip holder rotation unit 54 that rotates the chip holder 53; thepipetting unit 90 that injects target liquid into the injection port 22of the analysis chip 10; and the measurement unit 80 that allowsmeasurement of reactions between the target liquid and multiple types ofantigens 30 collectively. By making the chip holder rotation unit 54rotate the chip holder 53, the target liquid having been introduced intothe micro-flow path 23 is discharged. Thus, in an analysis device thatanalyzes target liquid having strong surface tension using themicro-flow paths 23, the target liquid can be discharged rapidly andreliably.

In the biochemical analysis device 50, the chip holder 53 includes thefitting part 531 to make a fit with the analysis chip 10. Thus, theanalysis chip 10 can reliably be fixed to the chip holder 53, therebypreventing falling off of the analysis chip 10 from the chip holder 53to be caused by centrifugal force during rotation.

Further, the analysis chip 10 placed at the chip holder 53 can berotated properly at a given speed. Additionally, the analysis chip 10 isinstalled on the chip holder 53 with temperature adjusting means. Thus,in an analysis device such as that of this embodiment requiringincubation under a constant temperature, an increased area of contactbetween the analysis chip 10 and the chip holder 53 achieves morereliable temperature adjusting control.

In the biochemical analysis device 50, the pipetting unit 90 injectstarget liquid while the chip holder rotation unit 54 rotates the chipholder 53. Thus, the liquid can be introduced uniformly into theplurality of micro-flow paths 23 connected to the injection port 22.This can prevent the occurrence of a situation where the liquid isintroduced unevenly into some of the micro-flow paths 23 or targetliquid of a necessary amount cannot be introduced into some of themicro-flow paths 23. As a result, even if the tip portion of thepipetting nozzle 92 (tip of the pipette chip 95) at the liquid injectionposition deviates from the center of rotation or even if the analysischip 10 is not placed in a horizontal posture, distances to respectiveliquid inlets of the micro-flow paths 23 can be substantially equal inresponse to rotation during the injecting process. This reducesinfluence on the injecting process by an error of accuracy of the shapeof the pipette chip 95 or attachment condition of the pipette chip 95,so that the injecting process can be performed properly.

In the biochemical analysis device 50, the pipetting unit 90 has thepipette chip 95 of a tapered shape. With the pipette chip 95 beinginserted into the injection port 22, the pipetting unit 90 injectstarget liquid. This prevents flying-off of the target liquid over theupper surface of the substrate 20 or its periphery or blockage of theinjection port 22 with droplets of the target liquid. As a result, thetarget liquid can be introduced rapidly into the micro-flow path 23through the injection port 22.

The biochemical analysis device 50 includes the air nozzle unit 100 thatinjects air into the injection port 22. This air and rotation of thechip holder 53 work in combination to reliably discharge target liquidin the micro-flow path 23 formed in the analysis chip 10.

The biochemical analysis device 50 makes the air nozzle unit 100 injectair into the analysis chip 10 while rotating the chip holder 53. Thus,even if target liquid is left unremoved in the micro-flow path 23 by thepresence of strong surface tension in the micro-flow path 23, suchtarget liquid can reliably be discharged from the micro-flow path 23with air injected from the air nozzle unit 100.

The present invention is not limited to each aspect of the preferredembodiment of the analysis chip 10 and that of the preferred embodimentof the biochemical analysis device 50 of the present invention describedabove. Various changes can certainly be devised based on the principlesof the present invention.

According to the configuration of this invention, the liquid injectionposition is set in such a manner that the tip of the pipette chip 95substantially agrees with the center of rotation of the chip holder 53.However, the liquid injection position can be set in differentappropriate ways. According to a modification described next, the liquidinjection position is set in such a manner that the tip of the pipettechip 95 from which target liquid is injected deviates from the center ofrotation of the chip holder 53. FIG. 15 is a schematic view illustratinga state in outline where the pipetting unit 90 of a biochemical analysisdevice according to the modification is injecting target liquid into theanalysis chip 10. Illustrations of structures of the analysis chip 10except the substrate 20 are omitted from FIG. 15. Illustrations of thestructures of the biochemical analysis device 50 including the chipholder 53 are also omitted.

As illustrated in FIG. 15, according to the modification, the tip sideof the pipette chip 95 from which liquid is pipetted is set at aposition deviating from the center of rotation of the chip holder 53.This can be rephrased as follows. As described above, the substrate 20provided in the analysis chip 10 of this embodiment includes a pluralityof micro-flow paths 23 arranged in a radial pattern with respect to theinjection port 22. Respective entrances of the micro-flow paths 23 arelocated at equally-spaced positions from the center of the injectionport 22. A liquid injection position of this modification is set at aposition deviating from these equally-spaced positions. The pipette chip95 at the liquid injection position is arranged adjacent to theinjection port 22 so as to make liquid pipetted from the tip of thepipette chip 95 contact the inner side surface of the injection port 22.The tip of the pipette chip 95 at the liquid injection position is setso as to be placed below the upper surface of the substrate 20 and so asto form a gap between the tip of the pipette chip 95 and the bottomsurface of the injection port 22. Liquid is pipetted toward the chipholder 53 being rotated while the tip of the pipette chip 95 is placedat the liquid injection position. The tip side of the pipette chip 95 atthe liquid injection position is approximated in advance to the innerside surface of the injection port 22. Thus, liquid can be injecteduniformly and properly into the entrances of the plurality of micro-flowpaths 23 formed at the inner side surface of the injection port 22.

A modification using an analysis chip 210 having a differentconfiguration from the analysis chip 10 of the aforementioned embodimentis described next. FIG. 16 is a plan view illustrating the analysis chip210 according to the modification. FIG. 17 is a side sectional viewschematically illustrating the configuration of the inside of theanalysis chip 210 according to the modification. A biochemical analysisdevice 50 using the analysis chip 210 has the same configuration as thatof the aforementioned embodiment.

The analysis chip 210 of the modification includes a first substrate220, a second substrate 230, an absorber 215, liquid trapping space 216,an air communication opening 217, and a rotation position reference mark250.

The first substrate 220 is formed into a disc shape. A circular columnarstage part 241 is formed at the center of the first substrate 220. Awall part 242 is formed to extend over the entire periphery of an endsurface of the first substrate 220.

The second substrate 230 is formed into a disc shape using alight-transmitting material. The second substrate 230 is bonded to anupper part of the first substrate 220. A circular injection port 222 forinjection of various types of liquid is formed at the center of thesecond substrate 230. The injection port 222 is formed into a smallerdiameter than the stage part 241. Thus, the injection port 222 isaccommodated inside the stage part 241 in a plan view. A lower part ofthe injection port 222 of the second substrate 230 is formed into atapered shape in a side view that expands further radially at a positioncloser to the stage part 241 of the first substrate 220.

The upper surface of the stage part 241 of the first substrate 220 andthe lower surface of the second substrate 230 form a gap therebetween.The liquid having been injected through the injection port 222 isintroduced to the gap by means of capillary action. This gap is formedto extend over the entire outer periphery of the injection port 222.This gap functions as a flow path 255 of the analysis chip 210. In thisway, the flow path 255 of the analysis chip 210 is formed into aring-like shape surrounding the outer periphery of the injection port222. Thus, the flow path 255 of the analysis chip 210 of thismodification can be expressed as a single flow path 255.

In this modification, multiple types of antigens 30 are fixed to theflow path 255 to be close to the stage part 241. The multiple types ofantigens 30 are arranged at given intervals in a concentric circularpattern surrounding the injection port 222. The antigens 30 are alignedso as not to overlap each other at least at their centers in a radialdirection. By doing so, a distance between the antigens 30 is maintainedproperly, so that an image of light-emitting reaction can be capturedwith a high resolution.

Aligning the antigens 30 in the concentric circular pattern is not theonly method of fixing the antigens 30. For example, multiple types ofantigens 30 may also be arranged irregularly in the flow path 255 of theanalysis chip 210 according the modification. Alternatively, a partitionmay be provided to a part of the flow path 255 to divide the flow path255 into sector forms. Still alternatively, the antigens 30 may be fixedto the flow path 255 to be close to the second substrate 230. Asdescribed above, the method of arranging the antigens 30 can also bechanged in this modification.

The absorber 215 is formed of a member having moisture-retainingproperties. The absorber 215 is formed into a ring-like shape of alarger diameter than the stage part 241. The liquid trapping space 216is formed inside the analysis chip 210 to surround the outer peripheralsurface of the stage part 241. The absorber 215 is arranged in theliquid trapping space 216 so as to surround the outer peripheral surfaceof the stage part 241. Target liquid having been discharged from theflow path 255 by means of centrifugal force resulting from rotation ofthe analysis chip 210 or injection of air by the air nozzle unit 100 isdischarged to the liquid trapping space 216 and absorbed by the absorber215.

The air communication opening 217 includes a plurality of aircommunication openings 217 formed outside the stage part 241 in a planview. Air having been injected by the air nozzle unit 100 and havingpassed through the air communication openings 217 is discharged from theinside of the analysis chip 210 to the outside of the analysis chip 210.An air communication opening 217 a belonging to the plurality of aircommunication openings 217 lies on a virtual straight line connectingthe center of the analysis chip 210 and the rotation position referencemark 250 to be placed at a position adjacent to the rotation positionreference mark 250.

The rotation position reference mark 250 is an indication used fordetecting the orientation of the analysis chip 210 and is provided tothe first substrate 220. The rotation position reference mark 250 ofthis modification is provided at one position at the edge of the stagepart 241 and has a semicircular shape. The number of the rotationposition reference marks 250, and the location and the shape of therotation position reference mark 250 can be changed, if appropriate. Forexample, the rotation position reference mark 250 can be provided to thesecond substrate 230.

The rotation position reference mark 250 is stored in advance in thestorage of the control unit 110 as arrangement state determinationinformation corresponding to information about the shape of the analysischip 210 to be used for identifying a rotation position. Based on theposition of the rotation position reference mark 250 in imageinformation acquired by the measurement unit 80 and the arrangementstate determination information, the control unit 110 determines theorientation of the rotated analysis chip 210.

In this modification, a positioning notch 280 is formed in each of thefirst substrate 220 and the second substrate 230. The positioning notch280 is used for determining the positions of the first substrate 220 andthe second substrate 230 when the first substrate 220 and the secondsubstrate 230 are adhesively joined during a step of manufacturing theanalysis chip 210. The positioning notches 280 of this modification areformed at positions facing each other across the center of the analysischip 210. The first substrate 220 and the second substrate 230 areadhesively joined at proper positions determined by the respectivepositioning notches 280 formed in the first substrate 220 and the secondsubstrate 230. Further, the air communication opening 217 a formed inthe second substrate 230 is adjacent to the rotation position referencemark 250. Thus, whether or not the first substrate 220 and the secondsubstrate 230 are in their proper positions can also be determined byusing the air communication opening 217 a.

The analysis chip 210 of this modification has the aforementionedconfiguration. The biochemical analysis device 50 analyzes target liquidusing the analysis chip 210. Target liquid such as an analyte enters theflow path 255 through the injection port 222 and is introduced into theflow path 255 from an inner side toward an outer side by means ofsurface tension.

A method of injecting target liquid such as an analyte into the analysischip 210 and a method of measuring reaction with the antigen 30 are thesame as the aforementioned methods. In this modification, theorientation of the rotated analysis chip 210 can be determinedaccurately based on the rotation position reference mark 250. The typeof each reaction is measured based on position information about themultiple types of antigens 30 fixed to the analysis chip 210. Theposition information about the antigens 30 is information set inadvance.

As described above, the analysis chip 210 is formed in such a mannerthat the flow path 255 surrounds the outer periphery of the injectionport 222. By doing so, space around the injection port 222 can be usedfor arrangement of many types of antigens 30. Further, manufacturingcost can be reduced as a result of a simple configuration of forming theflow path 255 around the injection port 222.

The configuration of the analysis chip 210 according to the modificationcan be changed, if appropriate. For example, the analysis chip 210 mayinclude a housing to hold the first substrate 220 and the secondsubstrate 230. In this case, the wall part 242 can be omitted from thefirst substrate 220 and liquid trapping space can be arranged inside thehousing and on the outer peripheries of the first substrate and thesecond substrate. Alternatively, the analysis chip 210 of themodification may include a housing same as the housing of theaforementioned embodiment (including the lower housing 12 and the upperhousing 13) and may include an air communication opening in a gapbetween the housing and the second substrate.

In the biochemical analysis device 50 of this embodiment, the chipholder rotation unit 54 includes the temperature adjustment unit insidethe chip holder rotation unit 54. However, the location of a temperatureadjustment unit can be changed, if appropriate. For example, atemperature adjustment unit may be provided inside the dark box 81.Additionally, a temperature adjustment unit may be arranged in the darkbox 81 in addition to the temperature adjustment unit arranged in thechip holder rotation unit 54. By doing so, the temperature of theanalysis chip 10 may be adjusted using a plurality of temperatureadjustment units.

The biochemical analysis device 50 of this embodiment can employ anappropriate method of measuring the antigen 30 placed in the micro-flowpath 23 of the analysis chip 10 at the measurement position. Forexample, based on the frequency of rotation of the drive motor forrotating the chip holder 53, reaction may be measured by estimating anddetermining the arrangement state of the antigen 30 after operation ofrotating the analysis chip 10.

In the biochemical analysis device 50 of this embodiment, the amount ofsuction of target liquid by the pipetting unit 90 is set in a mannerthat depends on the type of the target liquid. However, thisconfiguration can be changed, if appropriate. For example, theconcentration of a reagent solution may be adjusted and the amount ofsuction (or the amount of injection into the analysis chip 10) may bekept at a constant amount.

The biochemical analysis device 50 of this embodiment is configured toinject air using the air nozzle unit 100 in the liquid dischargingprocess. However, this air injecting process can be omitted in a mannerthat depends on an analysis target such as an analyte.

The configuration of the analysis chip 10 of this embodiment is suchthat the antigen 30 as a reactant to react with target liquid is fixedto the substrate 20. Alternatively, an antibody may be fixed. In thisway, a reactant to be fixed to the substrate of the analysis chip can bechanged, if appropriate, as long as the reactant is a substance to reactwith target liquid.

The configuration of the analysis chip 10 of this embodiment is notlimited to that described in this embodiment but can be changed, ifappropriate. For example, the micro-flow paths 23 can be arranged atpositions not symmetric with each other.

The configuration of the analysis chip 10 of this embodiment is suchthat the absorber 15 is arranged in the liquid trapping space 16.However, this configuration can be changed, if appropriate. For example,the analysis chip 10 may also be configured in such a manner that theliquid trapping space 16 is given a structure of trapping liquid andthis trapping structure functions to prevent liquid having beendischarged from the micro-flow path 23 from returning back into themicro-flow path 23. The analysis chip 10 may also be configured in sucha manner that numerous slits are formed in the bottom surface of theliquid trapping space 16 and liquid having been discharged from themicro-flow path 23 is caused to stay in the liquid trapping space 16 bythese slits. Alternatively, the absorber 15 may be omitted from theconfiguration of the analysis chip 10. As described above, a structurefor trapping liquid in the liquid trapping space 16 can be changed, ifappropriate.

The configuration of the substrate 20 provided in the analysis chip 10of this embodiment is not limited to the configuration described in thisembodiment. The substrate can be formed of a plurality of members. Forexample, the configuration of the substrate 20 may be such that themicro-flow path 23 is formed by fixing a substrate of a substantiallydisc shape instead of arranging the film 14 on the lower surface of thesubstrate 20. As described above, an appropriate configuration can beemployed for the substrate 20.

In the description of this embodiment given above, the biochemicalanalysis device 50 is described as an example of a sample analysisdevice. However, the present invention is not limited to the biochemicalanalysis device 50 but is applicable to various types of sample analysisdevices. For example, the present invention is also applicable to asample analysis device to detect trace metal, for example.

EXPLANATION OF REFERENCE NUMERALS

-   -   10 Analysis chip    -   12 Lower housing (housing)    -   13 Upper housing (housing)    -   16 Liquid trapping space    -   17 Air communication opening (communication opening)    -   18 Opening part    -   20 Substrate    -   22 Injection port    -   23 Micro-flow path (flow path)    -   30 Antigen (reactant)    -   50 Biochemical analysis device (sample analysis device)    -   53 Chip holder    -   54 Chip holder rotation unit (chip holder rotation mechanism)    -   80 Measurement unit (measurement device)    -   90 Pipetting unit (pipetting mechanism)    -   92 Pipetting nozzle    -   95 Pipette chip (tip portion)    -   100 Air nozzle unit (Air injection mechanism)    -   110 Control unit (controller)    -   210 Analysis chip    -   216 Liquid trapping space    -   220 First substrate (substrate)    -   222 Injection port    -   230 Second substrate (substrate)    -   255 Flow path

The invention claimed is:
 1. A sample analysis device comprising: a chipholder configured to have an analysis chip installed thereon, theanalysis chip comprising a substrate, an injection port formed at thesubstrate and through which target liquid as a measurement target isinjected, a flow path connected to the injection port and allowingintroduction of the target liquid into the flow path by means ofcapillary action, and a plurality of reactants, each of which is fixedat a position to a surface of the flow path, the plurality of reactantsbeing capable of selectively reacting with a component in the targetliquid; a chip holder rotation mechanism configured to rotate the chipholder; a pipetting mechanism configured to inject the target liquidinto the injection port of the analysis chip; and a measurement deviceconfigured to measure reactions between the target liquid and theplurality of reactants, wherein the pipetting mechanism is furtherconfigured to inject the target liquid while the chip holder rotationmechanism rotates the chip holder.
 2. The sample analysis deviceaccording to claim 1, wherein the pipetting mechanism has a tip portionof a tapered shape, and the pipetting mechanism injects the targetliquid with the tip portion being inserted into the injection port. 3.The sample analysis device according to claim 1, wherein the injectionport of the analysis chip is formed at the center of the substrate. 4.The sample analysis device according to claim 1, wherein the flow pathof the analysis chip includes a plurality of flow paths arranged in aradial pattern to extend from the injection port to an outer edge of thesubstrate, and the plurality of reactants capable of selectivelyreacting with a component in the target liquid is fixed to each of theflow paths.
 5. The sample analysis device according to claim 1, whereinthe analysis chip is formed in such a manner that the flow pathsurrounds the injection port.
 6. The sample analysis device according toclaim 1, further comprising an air injection mechanism that injects airinto the injection port of the analysis chip.
 7. The sample analysisdevice according to claim 6, wherein the air injection mechanism injectsair into the analysis chip while the chip holder is rotated.
 8. Thesample analysis device according to claim 6, wherein the analysis chipfurther comprises a housing in which the substrate is arranged andhoused, and the housing includes: an opening part where an upper surfaceof the substrate is exposed at least partially; liquid trapping spaceprovided inside the housing and on an outer peripheral side of thesubstrate; and a communication opening formed around the opening partand between the upper surface of the substrate and the housing.
 9. Thesample analysis device according to claim 8, wherein the communicationopening is arranged inwardly in a radial direction from the outerperiphery of the substrate.